2. Academic Validation
  3. New Quinoline Kinase Inhibitors With Good Selectivity for NAK Kinases and Anti-Tumor Activity Against Ewing Sarcoma

New Quinoline Kinase Inhibitors With Good Selectivity for NAK Kinases and Anti-Tumor Activity Against Ewing Sarcoma

  • Arch Pharm (Weinheim). 2026 Jan;359(1):e70184. doi: 10.1002/ardp.70184.
Caroline de Bem Gentz 1 2,  Thais Helena Maciel Fernandes 1 2,  Marcela Silva Lopes 3 4,  Lewis Elson 5,  Andreas Krämer 5,  Lucas Rodrigo de Souza 6,  Isadora Serraglio Fortes 1 2 4,  Geórgia Silva Pinto 2,  Martha Cestari Silva Martins 1 2,  Henrique Barros de Lima 1 2,  André da Silva Santiago 6,  Lauro José Gregianin 4 7 8 9,  Katlin Brauer Massirer 6,  Mário Henrique Bengtson 6,  Rafael Roesler 3 4 7,  Stefan Knapp 5,  Stefan A Laufer 10,  Saulo Fernandes de Andrade 1 2 4
Affiliations

Affiliations

  • 1 Pharmaceutical Sciences Graduate Program, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
  • 2 Pharmaceutical Synthesis Group (PHARSG), School of Pharmacy, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
  • 3 Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
  • 4 National Science and Technology Institute for Children's Cancer Biology and Pediatric Oncology - INCT BioOncoPed, Porto Alegre, Brazil.
  • 5 Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt, am Main, Germany.
  • 6 Center for Medicinal Chemistry (CQMED), Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
  • 7 Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
  • 8 Department of Pediatrics, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
  • 9 Pediatric Oncology Service, Clinical Hospital, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
  • 10 Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, University of Tübingen, Tübingen, Germany.
PMID: 41518355 DOI: 10.1002/ardp.70184
Abstract

In the past few years, several novel Anticancer agents targeting protein kinases have been discovered expanding the available therapeutic arsenal. However, few new therapeutic approaches have been developed for the treatment of childhood Cancer. To this end, we have been making efforts to contribute to this important field. Herein, we identified a series of new 4,6-disubstituted quinoline derivatives from our in-house quinoline chemical library that showed promising anti-proliferative activity against Ewing Sarcoma (ES). This interesting observation engaged us to further investigate these derivatives since this type of Cancer is among the most common bone cancers in children. Evaluation of the quinoline derivatives against a panel of kinases demonstrated generally narrow selectivity profiles of this compound class. Interestingly, the main kinases that were inhibited belonged to the NAK family of kinases, in particular, the family member cyclin G-associated kinase (GAK) which was inhibited at nanomolar range in enzyme kinetic assays.

Keywords

Ewing Sarcoma; GAK; inhibitor; panel of kinases; quinoline.

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